vitamin-k-semiquinone-radical and Stomach-Neoplasms

Several authors have reported the relationship between gastric cancer risk and vitamins. However, there are few reports on fat-soluble vitamins after gastrectomy for gastric cancer. Fat malabsorption and suppression of food intake after gastrectomy for gastric cancer have been previously documented. Because of fat malabsorption and suppression of food intake, a potential deficiency in fat-soluble vitamins, such as vitamins A, D, E, and K, has been readily suggested. In about 20 % of patients, the serum vitamin E levels were decreased. Indeed, vitamin E deficiency is a common complication after gastrectomy. Continuous vitamin E deficiency could develop from neurological symptoms, i.e., peripheral neuropathy, limb or truncal ataxia. The total cholesterol level is associated with the vitamin E levels. However, the serum vitamin A levels were decreased in only 1.8 % of patients. In total gastrectomy cases, the serum vitamin A level may readily decrease. In contrast, 1,25(OH)

Topics: Gastrectomy; Humans; Postoperative Complications; Stomach Neoplasms; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin E; Vitamin E Deficiency; Vitamin K

Activation of tyrosine kinases is an important factor during cancer development. Axl, one of the receptor tyrosine kinases, binds to the specific ligand growth arrest-specific gene 6 (Gas6), which encodes a vitamin K-dependent gamma-carboxyglutamyl protein. Although many receptor tyrosine kinases and their ligands are involved in gastric carcinogenesis, whether Gas6-Axl signaling is involved in gastric carcinogenesis has not been elucidated. The aim of this study was to investigate the expression of Gas6 and Axl in gastric cancer and also their roles during gastric carcinogenesis. mRNA and protein of Gas6 and Axl were highly expressed in a substantial proportion of human gastric cancer tissue and cell lines, and Gas6 expression was significantly associated with lymph node metastasis. With recombinant Gas6 and a decoy-receptor of Axl in vitro, we demonstrated that Gas6-Axl signaling pathway enhanced cellular survival and invasion and suppressed apoptosis via Akt pathway. Our results suggests that Gas6-Axl signaling plays a role during gastric carcinogenesis, and that targeting Gas6-Axl signaling could be a novel therapeutic for gastric cancer.

Topics: Axl Receptor Tyrosine Kinase; Base Sequence; Cell Line, Tumor; Cell Survival; DNA Primers; Gene Expression Regulation, Neoplastic; Humans; Immunoprecipitation; Intercellular Signaling Peptides and Proteins; Oncogene Proteins; Phosphorylation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptor Protein-Tyrosine Kinases; Stomach Neoplasms; Vitamin K

Although it is widely known that the extracellular signal-regulated kinase (ERK) pathway stimulates cell growth and protects cells from death, recent findings have proposed a proapoptotic action of ERK phosphorylation. Because the authors found that vitamin K3 (VK3) was a potent growth inhibitor and an inducer for ERK phosphorylation through a specific pathway in the stomach cancer cell line, the critical role of ERK phosphorylation in VK(3)-mediated growth inhibitory effect was examined.. The fluorochrome Hoechst 33258 assay (Hoechst AG [now Aventis] Frankfort, Germany) was used for counting cells (excitation at 360 nm; emission at 460 nm). For two-dimensional electrophoresis, cells were dissolved in urea standard buffer and applied first to isoelectronic focusing gels. Cell lysates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using 10% polyacrylamide gels. To examine the phosphorylation of receptors, cell lysates were immunoprecipitated with receptor antibody.. VK3 induced phosphorylation of hepatocyte growth factor receptor (c-met), epidermal growth factor receptor (EGFR), or external signal-regulated kinase (ERK), which increased progressively to a maximum level at 30 minutes, in a dose-dependent manner and occurred at growth inhibitory concentrations. VK(3)-mediated growth inhibition and protein tyrosine phosphorylation were nullified completely by glutathione or L-cysteine but not by nonthiol antioxidants, thus suggesting that sulfhydryl arylation might have been involved in VK(3)-mediated action. The phosphorylation of EGFR and c-met by VK(3) appeared to be functional, because these were coimmunoprecipitated with growth factor receptor-bound protein 2 (Grb2) and SOS1 antibody. Epidermal growth factor (EGF) or hepatocyte growth factor (HGF) stimulated increase of cyclin D1 protein after 12 hours and increased DNA content after 3 days in culture. In addition, U0126, which is a potent inhibitor for ERK phosphorylation, antagonized increase of cyclin D1, thus suggesting that EGF- or HGF-mediated ERK phosphorylation might have played an essential role for cell growth. By contrast, ERK phosphorylation by VK3 was more prolonged and intense than the signal induced by the growth factors. U0126 reduced ERK phosphorylation and prevented growth inhibition by VK3. Two-dimensional gels showed VK(3)-induced additional phospho-ERK spots, compared with those obtained from growth factors. This extra spot was completely antagonized by U0126.. VK(3)-induced growth inhibition and protein tyrosine phosphorylation were mediated by the sulfhydryl arylation system. The tyrosine phosphorylation of EGFR or c-met by VK3 activated the Ras signaling pathway. The overexpressed ERK phosphorylation by VK3 seemed to originate from additional spots on two-dimensional gels, which played a critical role in VK(3)-induced growth inhibitory action despite the fact that ERK phosphorylation by growth factors had had an essential association with cell growth.

Topics: Apoptosis; Cell Division; ErbB Receptors; Gene Expression Regulation; Humans; Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-met; Signal Transduction; Stomach Neoplasms; Tumor Cells, Cultured; Vitamin K

Topics: Adenocarcinoma; Aged; Atrial Fibrillation; Blood Transfusion; Cephalothin; Digoxin; Disseminated Intravascular Coagulation; Gangrene; Gastrointestinal Hemorrhage; Gentamicins; Heparin; Humans; Hydronephrosis; Hypothermia; Lymphatic Metastasis; Male; Prostatic Neoplasms; Pyelonephritis; Stomach Neoplasms; Vitamin K

Topics: Acute Disease; Ascorbic Acid; Blood Transfusion; Diet; Diet Therapy; Duodenal Ulcer; Endoscopy; Esophageal and Gastric Varices; Gastritis; Gastrointestinal Hemorrhage; Hematemesis; Hernia, Diaphragmatic; Humans; Melena; Myocardial Infarction; Peptic Ulcer Hemorrhage; Radiography; Stomach Neoplasms; Vagotomy; Vitamin K

Topics: Adult; Antineoplastic Agents; Arsenicals; Breast Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Choriocarcinoma; Colonic Neoplasms; Drug Synergism; Female; Fluorides; Heparin; Humans; Lung Neoplasms; Male; Malonates; Melanoma; Neoplasms; Ovarian Neoplasms; Pharyngeal Neoplasms; Pregnancy; Rectal Neoplasms; Sarcoma; Stomach Neoplasms; Testicular Neoplasms; Thyroid Neoplasms; Time Factors; Vitamin K

Topics: Adenocarcinoma; Adult; Aged; Animals; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Cystadenoma; Female; Humans; Iodine Radioisotopes; Kidney Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Mice; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Peritoneal Neoplasms; Radiation-Sensitizing Agents; Radionuclide Imaging; Rats; Rectal Neoplasms; Sigmoid Neoplasms; Stomach Neoplasms; Vitamin K

Topics: Analgesics; Bile Duct Neoplasms; Cholangiography; Cholelithiasis; Cysts; Dexamethasone; Gallbladder Neoplasms; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Penicillins; Postoperative Care; Prednisolone; Preoperative Care; Stomach Neoplasms; Vitamin K