Animals ; Brain ; embryology ; Ear ; embryology ; Esophagus ; embryology ; Fallopian Tubes ; embryology ; Female ; Heart ; embryology ; Humans ; Kidney ; embryology ; Liver ; embryology ; Lung ; embryology ; Male ; Organogenesis ; physiology ; Penis ; embryology ; Rabbits ; Stomach ; embryology ; Vagina ; embryology

OBJECTIVETo observe the regional homogeneity (ReHo) of resting-state brain function in the healthy subjects of gastric distention treated with acupuncture at the back- and front- points of the stomach, Weishu (BL 21) and Zhongwan (CV 12) and the correlation with gastric motility so as to explore the mechanism on the central integration of the front- and back- points of the stomach.

METHODSThe crossover test design was adopted. Twenty-four healthy subjects were assigned to a Weishu group, a Zhongwan group and a combined-point group separately, 8 cases in each one in each of the three times. Totally, 24 subjects were included in each group. Under the water load condition, the subjects received acupuncture at Weishu (BL 21), Zhongwan (CV 12) and the combined Weishu (BL 21) and Zhongwan (CV 12). Before and after each acupuncture, the resting-state brain functional magnetic resonance imaging (fMRI) scan and electrogastrogram (EGG) test were applied. The ReHo value was calculated in the collected fMRI imaging data. The changes in ReHo values were analyzed and compared before and after acupuncture in each group, as well as among the groups. The gastric motility was analyzed before and after acupuncture. Additionally, the correlative analysis was conducted between the gastric motility and ReHo changes before and after acupuncture.

RESULTS(1) After acupuncture, EGG amplitudes in the subjects of each group were lower remarkably as compared with those before acupuncture (all <0.01). The EGG frequencies were not different significantly as compared with those before acupuncture (all >0.05). The EGG amplitudes in the Weishu group and the Zhongwan group were higher than those in the combined-point group (both <0.05). (2) As compared with the conditions before acupuncture, acupuncture at the combined front- and the back- points as well as Weishu (BL 21) and Zhongwan (CV 12) separately all induced the changes in the brain ReHo. Acupuncture at the combined front- and the back- points significantly increased Reho values in the right inferior temporal gyrus, the left thalamus, the precuneus and the posterior cingulate gyrus (all <0.05) and remarkably reduced the ReHo values in the the middle temporal gyrus of the right temporal pole, sulcus calcarinus and precuneus (all <0.05). Compared with the single point groups, acupuncture at the combined front- and the back- points induced the increase of ReHo value in the posterior cingulate gyrus and the decrease of ReHo in the temporal pole (all <0.05). (3) The correlative analysis showed that the changes in the ReHo values in the posterior cingulate gyrus, the thalamus and the precuneus were positively correlated to the changes of the gastric motility amplitudes. The changes in the ReHo values in the temporal pole was negatively correlated to the changes of the gastric motility amplitudes.

CONCLUSIONAcupuncture at the combined back- and front- points of the stomach, as well as acupuncture at single Weishu (BL 21) and Zhongwan (CV 12) induce the ReHo changes in the different brain regions. Acupuncture at the combined back- and front- points of the stomach may induce the ReHo changes in some new brain regions as compared with the acupuncture at the single point. The thalamus, the posterior cingulate gyrus and the precuneus may be the the important integrated brain regions for acupuncture at the back- and the front- points in regulating the gastric motility. The effects of acupuncture at the back- and the front- points for the regulation of the gastric motility are closely related to the thalamus, the limbic system and the default network of the brain regions.

Acupuncture Points ; Acupuncture Therapy ; Brain ; diagnostic imaging ; physiology ; Cross-Over Studies ; Electroencephalography ; Gastrointestinal Motility ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Stomach ; physiopathology

To explore the effect of high fat diet on proteome in mice stomachs, we constructed a model in which the mice were fed with high fat diet as the high fat diet (HFD) group or normal diet as the control (CTRL) group for 110 days. The stomachs were collected and divided into three regions (forestomach (F), corpus (C) and antrum (A)) for protein extraction and mass spectrometry analysis. Of all 9 307 identified proteins in two groups, 4 066 proteins (HFD: 3 832, CTRL: 3 654) were strictly identified by at least one unique peptide and identified twice in three replicates. Using gene ontology (GO) and interaction network analysis we analyzed differentially expressed proteins (fold change≥2) in two groups or between regions. In the whole stomach tissues, proteins up-regulated in HFD group mainly were associated with protein stabilization and protein transport. Differentially expressed proteins between regions showed that forestomach was related to the biological process of keratinization and actin assembly, while corpus and antrum mainly performed digestive function. Compared with forestomach, the corpus and antrum were more affected by the diet. Though there was no significant effect on the basic digestive function of the stomach, proteins that were involved in protein transport and lipid metabolism-related biological processes were significantly highly expressed in HFD group.
Animals ; Diet, High-Fat ; Lipid Metabolism ; Mice ; Mice, Inbred C57BL ; Protein Transport ; Proteome ; physiology ; Stomach ; physiology

BACKGROUND/AIMS: Gastric juice plays a crucial role in the physiology of the stomach. The aim of this study is to evaluate associations among the pH of gastric juice, atrophic gastritis (AG), intestinal metaplasia (IM), pepsinogen, and Helicobacter pylori infection. METHODS: Gastric biopsies and juice were collected from 46 subjects who underwent endoscopies at Seoul National University Bundang Hospital between November 2011 and March 2013. H. pylori, AG and IM were evaluated, and pepsinogen I or II, I/II ratio, and interleukin (IL)-1β levels were measured. RESULTS: The mean pH of gastric juice was higher in the H. pylori-positive group (n=17) than that in the H. pylori-negative group (n=29) (4.54 vs 2.46, p=0.002). When patients were divided into pH < 3 (n=28) and pH ≥3 (n=18) groups, H. pylori was lower in the pH < 3 group (21.4%) than in the pH ≥3 group (61.1%) (p=0.007). The pH ≥3 group demonstrated AG and IM more frequently than the pH < 3 group in the body (p=0.047 and p=0.051, respectively) but not in the antrum. There were no differences in pepsinogen I or II, I/II ratio, and IL-1β levels between the two groups. CONCLUSIONS: There is a relationship between chronic H. pylori infection and gastric juice pH ≥3, which may originate from AG and IM in the body.
Biopsy ; Gastric Juice* ; Gastritis ; Gastritis, Atrophic* ; Helicobacter pylori* ; Helicobacter* ; Humans ; Hydrogen-Ion Concentration* ; Interleukins ; Metaplasia* ; Pepsinogen A ; Physiology ; Seoul ; Stomach

PURPOSE: Studies on the physiology of the transposed stomach as an esophageal substitute in the form of a gastric pull-up or a gastric tube in children are limited. We conducted a study of motility and the pH of gastric esophageal substitutes using manometry and 24-hour pH measurements in 10 such patients. METHODS: Manometry and 24 hour pH studies were performed on 10 children aged 24 to 55 months who had undergone gastric esophageal replacement. RESULTS: Six gastric tubes (4, isoperistaltic; 2, reverse gastric tubes) and 4 gastric pull-ups were studied. Two gastric tubes and 4 gastric pull-ups were transhiatal. Four gastric tubes were retrosternal. The mean of the lowest pH at the midpoint of the substitute was 4.0 (range, 2.8–5.0) and in the stomach remaining below the diaphragm was 3.3 (range, 1.9–4.2). In both types of substitute, the difference between the peak and the nadir pH recorded in the intra-thoracic and the sub-diaphragmatic portion of the stomach was statistically significant (p < 0.05), with the pH in the portion below the diaphragm being lower. The lowest pH values in the substitute and in the remnant stomach were noted mainly in the evening hours whereas the highest pH was noted mainly in the morning hours. All the cases showed a simultaneous rise in the intra-cavitatory pressure along the substitute while swallowing. CONCLUSION: The study suggested a normal gastric circadian rhythm in the gastric esophageal substitute. Mass contractions occurred in response to swallowing. The substitute may be able to effectively clear contents.
Child* ; Circadian Rhythm ; Deglutition ; Diaphragm ; Gastric Stump ; Humans ; Hydrogen-Ion Concentration* ; Manometry* ; Physiology ; Stomach

Helicobacter pylori infection is related to the development of gastric diseases. Our previous studies showed that high thioredoxin-1 (Trx1) expression in H. pylori can promote gastric carcinogenesis. To explore the underlying molecular mechanisms, we performed an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis of stomach tissues from Mongolian gerbil infected with H. pylori expressing high and low Trx1. Differences in the profiles of the expressed proteins were analyzed by bioinformatics and verified using Western blot analysis. We found three candidate proteins, 14-3-3α/β, glutathione-S-transferase (GST), and heat shock protein 70 (HSP70), in high Trx1 tissues compared with low Trx1 tissues and concluded that cellular stress and redox activity-related proteins were involved in the pathogenesis of gastric cancer associated with H. pylori Trx1.
14-3-3 Proteins/physiology* ; Animals ; Computational Biology ; Gerbillinae ; Glutathione Transferase/physiology* ; HSP70 Heat-Shock Proteins/physiology* ; Helicobacter Infections/complications* ; Helicobacter pylori ; Oxidation-Reduction ; Stomach Neoplasms/etiology* ; Stress, Physiological ; Thioredoxins/physiology*

Gastric cancer (GC) is one of the most common tumor in the world, and remains a major public health problem and one of the leading causes of death. Recently many researches have demonstrated that systemic inflammatory response is associated with prognosis and response to therapy in gastric cancer, and the peripheral blood count test can partly reflect the systemic inflammatory response. Based on the peripheral blood count test, there are a lot of research regarding the relation between the platelet count (PLT), neutrophil, lymphocyte, white blood cell (WBC), neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio (PLR) with their prognostic role in gastric cancer. A high PLT and preoperative lymphocytopenia are both associated with increased lymph node metastasis, stage (III(+IIII(), serosal invasion (T3+T4) risk and poorer overall survival. Besides above, platelet monitoring following surgery can be applied to predict the recurrence for patients with GC that suffer preoperative high PLT but have restored PLT levels following resection. Moreover systemic inflammatory factors based on blood parameters, such as PLR, NLR and so on, have relation with the poor prognosis of patients with GC. Among them, high NLR is a negative predictor of prognosis in GC patients. However PLR remains inconsistent, while most researches demonstrated high PLR may be useful prognostic factor rather than independent prognostic factor. There are still some limitations which include various cut-off values, little of clinician attention, the uncertain mechanism, etc. Here we review the research progress in the prognostic role of the blood count test in gastric cancer.
Blood Cell Count ; methods ; statistics & numerical data ; Blood Platelets ; physiology ; Humans ; Inflammation ; blood ; diagnosis ; immunology ; Leukocyte Count ; statistics & numerical data ; Lymphatic Metastasis ; diagnosis ; immunology ; Lymphocyte Count ; statistics & numerical data ; Lymphopenia ; blood ; physiopathology ; Neoplasm Invasiveness ; immunology ; Neoplasm Recurrence, Local ; blood ; diagnosis ; Neoplasm Staging ; statistics & numerical data ; Neutrophils ; immunology ; Platelet Count ; statistics & numerical data ; Prognosis ; Stomach Neoplasms ; blood ; diagnosis ; immunology ; mortality ; Treatment Outcome

OBJECTIVETo investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.

METHODSThe effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.

RESULTSWith the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.

CONCLUSIONSThe PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.

Alprostadil ; analogs & derivatives ; pharmacology ; Angiogenesis Inducing Agents ; metabolism ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Cell Count ; methods ; Cell Line, Tumor ; drug effects ; physiology ; Cell Migration Assays ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Coculture Techniques ; Cyclooxygenase 2 ; pharmacology ; Dinoprostone ; metabolism ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; metabolism ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; physiology ; Humans ; Lactones ; pharmacology ; Neovascularization, Pathologic ; physiopathology ; Stomach Neoplasms ; physiopathology ; Sulfones ; pharmacology

BACKGROUND/AIMS: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. METHODS: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. RESULTS: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 high-grade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). CONCLUSIONS: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.
Aged ; Basic Helix-Loop-Helix Transcription Factors/genetics ; DNA Methylation ; Female ; Gastrectomy/methods ; Genes, APC/physiology ; Genes, mos/genetics ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasms, Second Primary/epidemiology/*genetics/pathology ; Proportional Hazards Models ; Risk Factors ; Stomach Neoplasms/genetics/*pathology/surgery ; Thrombomodulin/genetics

With the deeper research of the proliferation, invasion and metastasis mechanisms of the gastric cancer, targeted therapy has become a hot spot in this field. The exploration of targeted agents for gastric cancer is mainly concentrated upon the drugs that target human epidermal growth factor receptor (HER) family, the vascular endothelial growth factor (VEGF), the phosphatidylinositol 3-kinase-protein kinase/mammalian target of rapamycin (PI3K/mTOR) and the NF-κB signaling pathways. The targeted drugs relevant to HER family include the Cetuximab, Nimotuzumab, Matuzumab, Panitumumab and Erlotinib which are aimed at HER-1, the Trastuzumab, Pertuzumab and T-DM1 (trastuzumab emtansine) which are aimed at HER-2, and the Lapatinib and Afatinib which are the multi-target agents of HER. The agents which target VEGF signaling pathway include the anti-VEGF monoclonal antibody (Bevacizumab), the anti-VEGFR drugs (Ramucirumab, Apatinib, Sorafenib, Sunitinib and cediranib), and the recombinant fusion protein (Aflibercept). The LY294002, BEZ235 and Everolimus which are aimed at PI3K/mTOR signaling pathway have shown great promise. Bortezomib has been researched more as a new agent which targets NF-κB signaling pathway. Currently, only Trastuzumab, Ramucirumab and Apatinib have been completed the stage 3 clinical trials and succeeded. In future, researches should focus on multi-target agents or applications in combination treatment. This review collects the recent researches and the clinical trials to summarize the current state and progress of research on gastric cancer targeted therapy.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; Humans ; Molecular Targeted Therapy ; NF-kappa B ; drug effects ; physiology ; Phosphatidylinositol 3-Kinases ; Stomach Neoplasms ; therapy ; Vascular Endothelial Growth Factor A