Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy

Patrad, Elham; Khalighfard, Solmaz; Amiriani, Taghi; Khori, Vahid; Alizadeh, Ali Mohammad

doi:10.1007/s13402-022-00715-3

Cited by 14 publications

(8 citation statements)

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“…The presence of these different subtypes may explain why clinical trials of several novel therapeutic agents for GC during the past decade have reported unsuccessful results [22] . Clinical trials and prospective randomized studies still face unprecedented challenges, especially because GC patients have different histological and molecular subtypes of this cancer [23,24] . The identi cation of a combination of treatments is urgently needed to provide effective therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

LINC01224 promotes the Warburg effect in gastric cancer by activating the PI3K/AKT/mTOR/HIF-1α axis

Bin,

Liu,

et al. 2023

Preprint

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BACKGROUND: Gastric cancer (GC) is an aggressive malignancy, and patients with advanced-stage GC have high rates of morbidity. The long intergenic non-protein coding RNA 1224 (LINC01224) functions in the pathogenesis of many cancers. We performed in vitro and in vivo studies of the pathogenesis of GC to investigate the effects and mechanism of LINC01224 in this cancer. METHODS: qRT-PCR was used to measure the expression of LINC01224, and qRT-PCR and western blotting were used to measure the expression of genes in the PI3K/AKT/mTOR/HIF-1α axis (phosphoinositide 3-kinase [PI3K], AKT, mammalian target of rapamycin [mTOR], and hypoxia-inducible factor 1 [HIF-1α]) in GC cells. The function of LINC01224 in GC cells was determined using transfection experiments and measurements of cell viability, cell proliferation, colony formation, apoptosis, cell migration, and cell invasion. Glucose metabolism was evaluated using a glucose uptake assay and measurements of lactate. A tumor xenograft model was used to examine the effect of LINC01224 on GC growth in vivo. RESULTS:Up-regulation of LINC01224 in GC cells activated the PI3K/AKT/mTOR/HIF-1α axis and promoted aerobic glycolysis, thereby increasing cell viability, proliferation, migration, and invasion, and decreasing apoptosis. Down-regulation of LINC01224 had the opposite effects. CONCLUSION: LINC01224 promotes the in vitro and in vivo pathogenesis of GC due to upregulation of aerobic glycolysis by activation of the PI3K/AKT/mTOR/HIF-1α axis. These results imply that future studies of GC should examine the effect of targeting of LINC01224 as a treatment strategy.

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Section: Discussionmentioning

confidence: 99%

LINC01224 promotes the Warburg effect in gastric cancer by activating the PI3K/AKT/mTOR/HIF-1α axis

Bin,

Liu,

et al. 2023

Preprint

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“…In addition, heme iron is considered a critical factor for bacterial growth, such as H. pylori, the main established risk factor of non-cardia gastric cancer [40,41]. Furthermore, independently of iron, consumption of processed foods contributes to an increased intake of salt, satu-rated fats, cholesterol, polycyclic aromatic hydrocarbons (PAHs), and heterocyclic amines (HCAs), compounds that have also been described as potential carcinogens [42], that may affect different intracellular pathways related to proliferation, angiogenesis, inflammatory responses, or apoptosis [43]. Salt irritates the gastric mucosa rendering it more susceptible to chemical carcinogenesis and to H. pylori colonization [19,44].…”

Section: Discussionmentioning

confidence: 99%

Meat Intake, Cooking Methods, Doneness Preferences and Risk of Gastric Adenocarcinoma in the MCC-Spain Study

et al. 2022

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Background: The association of meat intake with gastric adenocarcinoma is controversial. We examined the relation between white, red, and processed meat intake and gastric adenocarcinoma, considering doneness preference and cooking methods, by histological subtype and anatomical subsite. Methods: MCC-Spain is a multicase–control study that included 286 incident gastric adenocarcinoma cases and 2993 controls who answered a food-frequency questionnaire. The association of gastric adenocarcinoma with meat intake, doneness preference and cooking methods was assessed using binary multivariate logistic regression mixed models and a possible interaction with sex was considered. Multinomial logistic regression models were used to estimate risk by tumor subsite (cardia vs. non-cardia) and subtype (intestinal vs. diffuse). Sensitivity analyses were conducted comparing models with and without data on Helicobacter pylori infection. Results: The intake of red and processed meat increased gastric adenocarcinoma risk (OR for one serving/week increase (95% CI) = 1.11 (1.02;1.20) and 1.04 (1.00;1.08), respectively), specifically among men and for non-cardia and intestinal gastric adenocarcinoma. Those who consume well done white or red meat showed higher risk of non-cardia (white: RRR = 1.57 (1.14;2.16); red: RRR = 1.42 (1.00;2.02)) and intestinal tumors (white: RRR = 1.69 (1.10;2.59); red: RRR = 1.61 (1.02;2.53)) than those with a preference for rare/medium doneness. Stewing and griddling/barbequing red and white meat, and oven baking white meat, seemed to be the cooking methods with the greatest effect over gastric adenocarcinoma. The reported associations remained similar after considering Helicobacter pylori seropositivity. Conclusions: Reducing red and processed meat intake could decrease gastric adenocarcinoma risk, especially for intestinal and non-cardia tumors. Meat cooking practices could modify the risk of some gastric cancer subtypes.

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“…Among these factors, chronic inflammation and oxidative stress are widely regarded as critical contributors to this process 10 . The overproduction of ROS and RNS resulting from H. pylori infection might modulate multiple intracellular signaling pathways, including nuclear factor‐kappa B (NF‐κB) and mitogen‐activated protein kinase (MAPK), resulting in gastric carcinogenesis 2,11–13 . For a comprehensive understanding of the specific molecules involved in H. pylori ‐induced ROS production and inflammation response, readers are encouraged to consult previously published reviews 2,11–13 .…”

Section: Introductionmentioning

confidence: 99%

“…10 The overproduction of ROS and RNS resulting from H. pylori infection might modulate multiple intracellular signaling pathways, including nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), resulting in gastric carcinogenesis. 2,[11][12][13] For a comprehensive understanding of the specific molecules involved in H. pylori-induced ROS production and inflammation response, readers are encouraged to consult previously published reviews. 2,[11][12][13] Within this review, we offer a thorough analysis of the key factors connecting the host and H. pylori, including the host's response to generate ROS, H. pylori's strategies to counteract ROS, and the implications of persistent oxidant stress in host cells, such as DNA damage, lipid peroxidation, and protein oxidation.…”

Section: Introductionmentioning

confidence: 99%

“…2,[11][12][13] For a comprehensive understanding of the specific molecules involved in H. pylori-induced ROS production and inflammation response, readers are encouraged to consult previously published reviews. 2,[11][12][13] Within this review, we offer a thorough analysis of the key factors connecting the host and H. pylori, including the host's response to generate ROS, H. pylori's strategies to counteract ROS, and the implications of persistent oxidant stress in host cells, such as DNA damage, lipid peroxidation, and protein oxidation. These findings are critical for developing novel strategies to treat gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host

Wu,

Chen,

Chen

et al. 2023

Helicobacter

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Helicobacter pylori (H. pylori) is a highly successful human pathogen that colonizes stomach in around 50% of the global population. The colonization of bacterium induces an inflammatory response and a substantial rise in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), mostly derived from host neutrophils and gastric epithelial cells, which play a crucial role in combating bacterial infections. However, H. pylori has developed various strategies to quench the deleterious effects of ROS, including the production of antioxidant enzymes, antioxidant proteins as well as blocking the generation of oxidants. The host's inability to eliminate H. pylori infection results in persistent ROS production. Notably, excessive ROS can disrupt the intracellular signal transduction and biological processes of the host, incurring chronic inflammation and cellular damage, such as DNA damage, lipid peroxidation, and protein oxidation. Markedly, the sustained inflammatory response and oxidative stress during H. pylori infection are major risk factor for gastric carcinogenesis. In this context, we summarize the literature on H. pylori infection‐induced ROS production, the strategies used by H. pylori to counteract the host response, and subsequent host damage and gastric carcinogenesis.

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Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy

Cited by 14 publications

References 372 publications

LINC01224 promotes the Warburg effect in gastric cancer by activating the PI3K/AKT/mTOR/HIF-1α axis

LINC01224 promotes the Warburg effect in gastric cancer by activating the PI3K/AKT/mTOR/HIF-1α axis

Meat Intake, Cooking Methods, Doneness Preferences and Risk of Gastric Adenocarcinoma in the MCC-Spain Study

Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host

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