Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Function of tumor necrosis factor alpha before and after mutation in gastric cancer.

ABSTRACT:

Purpose

To explore the cause of functional changes of tumor necrosis factor alpha (TNF-α) in development of gastric cancer through the structural changes of each site in TNF-α before and after mutation.

Methods

Three typical mutant sites (TNF-α-308G/A, 857C/T and 863C/A of TNF-α) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-α before and after mutation, besides, the structural changes were also analyzed.

Results

Mutation of TNF-α-308G/A led to the production of multiple helical structures and that of 863C/A caused the production of one helical structure in its adjacent region. Mutation of 857C/T, however, did not cause the change in the basic structure of TNF-α.

Conclusions

Structural changes of TNF-α may have a significant effect on development of gastric cancer.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5851903 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Function of tumor necrosis factor alpha before and after mutation in gastric cancer.

Zhang Xia X Wang Jianjun J Shao Huanzhang H Zhu Wenliang W

Saudi journal of biological sciences 20171123 8

<h4>Purpose</h4>To explore the cause of functional changes of tumor necrosis factor alpha (TNF-α) in development of gastric cancer through the structural changes of each site in TNF-α before and after mutation.<h4>Methods</h4>Three typical mutant sites (TNF-α-308G/A, 857C/T and 863C/A of TNF-α) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-α before and after mutation, besides, the structural changes were also analyzed.<h4>Results</h4>Mutation of TNF-α-308G/A ...[more]

PMID: 29551945

Similar Datasets

Relationship Between Tumor Necrosis Factor-α rs361525 Polymorphism and Gastric Cancer Risk: A Meta-Analysis.

Project description:Tumor necrosis factor (TNF)-α, a major part in inflammatory, infectious and tumor processes, and is pivotal at the early stages of gastric cancer. Relationship between its risk and TNF-α rs361525 polymorphism has been demonstrated, but remains conflicting and controversial. Therefore, a meta-analysis was conducted to more precisely estimate this relationship. PubMed, Web of Science, EMBASE and CNKI were comprehensively searched to find out relevant articles through October 5, 2017. The strength of the relationship was assessed using pooled odds ratios and 95% confidence intervals. Totally 20 articles were included involving 4,084 cases and 7,010 controls. No significant relationship between TNF-α rs361525 polymorphism and increased GC risk was found in the whole populations. Subgroup analyses uncovered TNF-α rs361525 polymorphism intensified the risk of GC among Asians under five models, but decreased the risk of GC among Caucasiansin the allelic and dominant models. Subgroup analysis by genotyping methods revealed increased risk for other methods. In conclusion, this meta-analysis suggests TNF-α rs361525 polymorphism is related to the risk of GC, especially for Asians.

| S-EPMC5962813 | biostudies-literature

The relationship between tumor necrosis factor-α polymorphisms and gastric cancer risk: An updated meta-analysis.

Project description:The aim of the present study was to evaluate the relationship between tumor necrosis factor-α (TNF-α) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta-analysis was performed to assess the association between TNF-α gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non-cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. TNF-α 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10-1.23)]. In analysis stratified by ethnicity, TNF-α 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02-1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79-1.18)]. The overall ORs (95% CIs) for TNF-α 857, TNF-α 1031 and TNF-α 863 were 1.13 (1.04-1.24), 0.94 (0.85-1.05) and 0.89 (0.78-1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF-α 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non-cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03-1.31)]. TNF-α 308 and TNF-α 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF-α 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF-α 1031 and TNF-α 863 were not significantly associated with gastric cancer risk.

| S-EPMC5526040 | biostudies-literature

Alteration in Serum Levels of Tumor Necrosis Factor Alpha is associated with Histopathologic Progression of Gastric Cancer

Project description:BackgroundThe role of inflammatory cytokines, such as tumor necrosis-α (TNF-α) and IL-8, in gastric carcinogenesis has been investigated, but their impact remains to be further elucidated.MethodsIn this study, we measured the serum concentrations of these cytokines and H. pylori serostatus in dyspeptic patients, presenting with normal mucosa (NM = 53), chronic gastritis (CG = 94), and gastric cancer (GC = 82), by ELISA.ResultsModerate levels of TNF-α were detected in the NM group (19.9 ± 19.5 pg/ml), which were nearly doubled in patients with CG (35.7 ± 28.0 pg/ml) and drastically declined in GC patients (1.8 ± 5.9 pg/ml). The serum levels of IL-8, however, were not statistically different amongst these three groups.ConclusionTNF-α serum concentration seemed to undergo up- and downregulation, when moving from NM to CG and from CG to GC, respectively. If confirmed in a prospective study, this cytokine can behave as a serum indicator of gastric inflammation and malignant transformation.

| S-EPMC9971713 | biostudies-literature

Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy.

Project description:Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine known to have contradictory roles in oncoimmunology. Indeed, TNFα has a central role in the onset of the immune response, inducing both activation and the effector function of macrophages, dendritic cells, natural killer (NK) cells, and B and T lymphocytes. Within the tumor microenvironment, however, TNFα is one of the main mediators of cancer-related inflammation. It is involved in the recruitment and differentiation of immune suppressor cells, leading to evasion of tumor immune surveillance. These characteristics turn TNFα into an attractive target to overcome therapy resistance and tackle cancer. This review focuses on the diverse molecular mechanisms that place TNFα as a source of resistance to immunotherapy such as monoclonal antibodies against cancer cells or immune checkpoints and adoptive cell therapy. We also expose the benefits of TNFα blocking strategies in combination with immunotherapy to improve the antitumor effect and prevent or treat adverse immune-related effects.

| S-EPMC7985780 | biostudies-literature

Loss-of-function mutation in myostatin reduces tumor necrosis factor alpha production and protects liver against obesity-induced insulin resistance.

Project description:ObjectiveInsulin resistance develops in tandem with obesity. Ablating myostatin (Mstn) prevents obesity, so we investigated if Mstn deficiency could improve insulin sensitivity. A loss-of-function mutation (Mstn(Ln)) in either one or both alleles of the Mstn gene shows how Mstn deficiency protects whole-body insulin sensitivity.Research design and methodsMstn(Ln/Ln) mice were weaned onto a high-fat diet (HFD) or standard diet. HFD-fed Mstn(Ln/Ln) mice exhibited high lean, low-fat body compositions compared with wild types. Wild-type and heterozygous and homozygous mutant mice were bled to determine basal levels of insulin, glucose, and homeostasis model assessment of insulin resistance. To evaluate postprandial insulin sensitivity between animals of a similar size, glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies were performed with heterozygous and homozygous mutant mice. Quantitative RT-PCR quantified TNF proportional, variant, IL-6, IL-1beta, F4/80, GPR43, and CD36 expression in muscle, fat, and liver. Histological analysis measured hepatosteatosis.ResultsHomozygous mutants were glucose tolerant and protected against overall insulin resistance compared with heterozygous mice. Hyperinsulinemic-euglycemic clamp studies revealed a dramatically improved glucose infusion rate, glucose disposal rate, and hepatic glucose production in 11-month-old Mstn(Ln/Ln) mice on an HFD. Improvements to muscle and liver insulin sensitivity (approximately 200-400%) correlated with 50-75% decreased tumor necrosis factor (TNF)alpha production and coincided with severe Mstn deficiency. Hepatosteatosis appeared to be ameliorated. Short-term treatment of Mstn(Ln/Ln) mice with recombinant Mstn led to increased plasma TNFalpha and insulin resistance.ConclusionsWe find that severe Mstn deficiency caused by Ln (lean) mutations in HFD-fed mice protects muscle and liver against obesity-induced insulin resistance.

| S-EPMC2671051 | biostudies-literature

Effect of interleukin-1β and tumor necrosis factor α gene silencing on mouse gastric cancer cell proliferation and migration.

Project description:The aim of the present study was to investigate the effect of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) gene co-silencing in mouse gastric cancer (GC) cells. Respectively, three pairs of liposome-encapsulated IL-1β and TNFα small interfering RNA (siRNA) were transfected into the mouse GC cell line MFC. The most effective siRNA, as identified by reverse transcription-polymerase chain reaction, was used for co-suppression of IL-1β and TNFα genes. The activities of cell proliferation, colony formation and migration were determined by the Cell Counting Kit 8 method, colony formation assay and Transwell assay, respectively. Protein array analysis was performed to identify the differentially expressed factors. The possible signaling pathways of the various factors targeting the genes were identified by pathway enrichment analysis using KOBAS 2.0. siRNA1 and siRNAc were the most effective interference sequences for IL-1β and TNFα, respectively. Following co-transfection of siRNA1 and siRNAc, the expression of IL-1β and TNFα was inhibited at the mRNA and protein levels, and the cell proliferation, colony forming and migration abilities were reduced (P<0.05). The expression of inflammatory factors, including chemokine ligand 5, cyclooxygenase-2, IL-6, transforming growth factor β, IL-17A, matrix metallopeptidase 9 and stromal cell-derived factor 1α were also inhibited (P<0.05). These factors are mainly involved in the rheumatoid arthritis pathway, the intestinal immune network for IgA production, the TNF signaling pathway and the inflammatory bowel disease pathway. IL-1β and TNFα gene silencing inhibits the proliferation and migration of MFC. The mechanisms may involve multiple inflammatory factors that participate in the signaling pathways of tumor tissue inflammation, the immune network and TNF.

| S-EPMC4812115 | biostudies-literature

Transmembrane tumor necrosis factor alpha attenuates pressure-overload cardiac hypertrophy via tumor necrosis factor receptor 2.

Project description:Tumor necrosis factor-alpha (TNF-α) plays an important pathogenic role in cardiac hypertrophy and heart failure (HF); however, anti-TNF is paradoxically negative in clinical trials and even worsens HF, indicating a possible protective role of TNF-α in HF. TNF-α exists in transmembrane (tmTNF-α) and soluble (sTNF-α) forms. Herein, we found that TNF receptor 1 (TNFR1) knockout (KO) or knockdown (KD) by short hairpin RNA or small interfering RNA (siRNA) significantly alleviated cardiac hypertrophy, heart dysfunction, fibrosis, and inflammation with increased tmTNF-α expression, whereas TNFR2 KO or KD exacerbated the pathological phenomena with increased sTNF-α secretion in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro, respectively, indicating the beneficial effects of TNFR2 associated with tmTNF-α. Suppressing TNF-α converting enzyme by TNF-α Protease Inhibitor-1 (TAPI-1) to increase endogenous tmTNF-α expression significantly alleviated TAC-induced cardiac hypertrophy. Importantly, direct addition of exogenous tmTNF-α into cardiomyocytes in vitro significantly reduced ISO-induced cardiac hypertrophy and transcription of the pro-inflammatory cytokines and induced proliferation. The beneficial effects of tmTNF-α were completely blocked by TNFR2 KD in H9C2 cells and TNFR2 KO in primary myocardial cells. Furthermore, we demonstrated that tmTNF-α displayed antihypertrophic and anti-inflammatory effects by activating the AKT pathway and inhibiting the nuclear factor (NF)-κB pathway via TNFR2. Our data suggest that tmTNF-α exerts cardioprotective effects via TNFR2. Specific targeting of tmTNF-α processing, rather than anti-TNF therapy, may be more useful for the treatment of hypertrophy and HF.

| S-EPMC7714153 | biostudies-literature

The Hajdu Cheney mutation sensitizes mice to the osteolytic actions of tumor necrosis factor α.

Project description:Hajdu Cheney syndrome (HCS) is characterized by craniofacial developmental abnormalities, acro-osteolysis, and osteoporosis and is associated with gain-of-NOTCH2 function mutations. A mouse model of HCS termed Notch2tm1.1Ecan harboring a mutation in exon 34 of Notch2 replicating the one found in HCS was used to determine whether the HCS mutation sensitizes the skeleton to the osteolytic effects of tumor necrosis factor α (TNFα). TNFα injected over the calvarial vault caused a greater increase in osteoclast number, osteoclast surface, and eroded surface in Notch2tm1.1Ecan mice compared with littermate WT controls. Accordingly, the effect of TNFα on osteoclastogenesis was greatly enhanced in cultures of bone marrow-derived macrophages (BMMs) from Notch2tm1.1Ecan mice when compared with the activity of TNFα in control cultures. TNFα induced the expression of Notch2 and Notch2 mutant mRNA by ∼2-fold, possibly amplifying the NOTCH2-dependent induction of osteoclastogenesis. The effect of TNFα on osteoclastogenesis in Notch2tm1.1Ecan mutants depended on NOTCH2 activation because it was reversed by anti-NOTCH2 negative regulatory region and anti-jagged 1 antibodies. The inactivation of Hes1 prevented the TNFα effect on osteoclastogenesis in the context of the Notch2tm1.1Ecan mutation. In addition, the induction of Il1b, but not of Tnfa and Il6, mRNA by TNFα was greater in Notch2tm1.1Ecan BMMs than in control cells, possibly contributing to the actions of TNFα and NOTCH2 on osteoclastogenesis. In conclusion, the HCS mutation enhances TNFα-induced osteoclastogenesis and the inflammatory bone-resorptive response possibly explaining the acro-osteolysis observed in affected individuals.

| S-EPMC6768656 | biostudies-literature

Anti Tumor Necrosis Factor Alpha Agents and Surgical Stress Response

Project description:Background: The immunologic response to stress is regulated by the cytokines. Anti-Tumor Necrosis Factor-α agents are antibodies directed against a key cytokine in the process angiogenesis and collagen synthesis. It is not known whether they intervene with surgical stress response increasing the rate of postoperative complications. Method: Un-blinded prospective, non-interventional cohort single centre study including all the patients with Crohn’s disease and Ulcerative Colitis undergoing abdominal surgery. Immunological and endocrinological parameters will measured in blood samples taken from these patients before and after surgery. Power calculations showed that 17 patients in each arm are needed.

| 2154083 | ecrin-mdr-crc

Vasculitis associated with tumor necrosis factor-α inhibitors.

Project description:ObjectiveTo describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors.Patients and methodsThis is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti-TNF-α therapy.ResultsOf 8 patients with vasculitis associated with anti-TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti-TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation.ConclusionCutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed.

| S-EPMC3538488 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data