Gastric cancer: Basic aspects

Duarte, Hugo; Gomes, Joana; Machado, José Carlos; Reis, Celso A.

doi:10.1111/hel.12523

Cited by 38 publications

(33 citation statements)

References 52 publications

(83 reference statements)

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“…Gastric neoplasms are characterized by a high degree of heterogeneity, which makes it challenging to identify which therapeutic agents should be brought to clinical trials [10]. Gastric adenocarcinoma, which comprises diffuse, intestinal, and well-differentiated subtypes is responsible for approximately 90% of gastric cancer cases [10]. Moreover, gastric cancer comprises four molecular subtypes, each of which involves distinct sets of molecular players and pathways.…”

Section: Cancer Dynamics and Evolution In Gastric Tumorsmentioning

confidence: 99%

“…Moreover, gastric cancer comprises four molecular subtypes, each of which involves distinct sets of molecular players and pathways. These subtypes are: (1) Epstein-Barr virus (EBV)-positive tumors that possess PIK3CA mutations and PD-L1/2 amplifications (interestingly, patients with EBV-positive gastric tumors have higher survival rates [11]); (2) genomically stable tumors with mutations in genes encoding E-cadherin and RHO-family GTPaseactivating proteins; (3) tumors with microsatellite instability and high mutation rates that impact oncogenic proteins 3; and (4) tumors with chromosomal instability giving rise to aneuploidies (as detected by intestinal histology), mutations in TP53, and focal amplifications of Ras proteins [10,12]. We have also previously highlighted the need to consider the BRCA1-and BRCA2-defective subgroups of gastric cancer [13].…”

Section: Cancer Dynamics and Evolution In Gastric Tumorsmentioning

confidence: 99%

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Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword

Mentis

Boziki

Grigoriadis

et al. 2019

Cell. Mol. Life Sci.

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Helicobacter pylori (H. pylori) infection affects an estimated 4.4 billion people globally. Moreover, H. pylori presents the most significant risk factor for gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and it is the first example of bacterial infection linked to carcinogenesis. Here, we contend that H. pylori research, which focuses on a cancer-causing pathogen resident in a relatively accessible organ, the stomach, could constitute an exemplar for microbial-related carcinogenesis in less tractable organs, such as the pancreas and lung. In this context, molecular biological approaches that could reap rewards are reviewed, including: (1) gastric cancer dynamics, particularly the role of stem cells and the heterogeneity of neoplastic cells, which are currently being investigated at the single-cell sequencing level; (2) mechanobiology, and the role of three-dimensional organoids and matrix metalloproteases; and (3) the connection between H. pylori and host pathophysiology and the gut microbiome. In the context of H. pylori's contribution to gastric cancer, several important conundrums remain to be fully elucidated. From among them, this article discusses (1) why H. pylori infection, which causes both gastric and duodenal inflammation, is only linked to gastric cancer; (2) whether a "precision oncomicrobiology" approach could enable a fine-tuning of the expression of only cancer-implicated H. pylori genes while maintaining beneficial H. pylori-mediated factors in extra-gastric tissues; and (3) the feasibility of using antibiotics targeting the microbial DNA damage system, which shares commonalities with mechanisms for human cell replication, as chemopreventives. Additional therapeutic perspectives are also discussed.

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Section: Cancer Dynamics and Evolution In Gastric Tumorsmentioning

confidence: 99%

Section: Cancer Dynamics and Evolution In Gastric Tumorsmentioning

confidence: 99%

Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword

Mentis

Boziki

Grigoriadis

et al. 2019

Cell. Mol. Life Sci.

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“…However, the prognosis of GC remains very poor in patients at a late stage. There are still many gaps in our knowledge of the initiation and progression of GC, 2 which urges us to explore novel molecular networks in the development of GC and its therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

MiR‐129‐5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression

Lin

et al. 2020

FASEB j.

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MicroRNAs (miRNAs) play important roles in posttranscriptional regulation and may serve as targets for the diagnosis and treatment of cancers. Nevertheless, a comprehensive understanding of miRNAs profiles in gastric cancer progression is still lacking. Here, we report that miR‐129‐5p is downregulated in gastric cancer by analyzing TCGA database (n = 41) and clinical tumor samples (n = 60). MiR‐129‐5p transfection suppressed gastric cancer cell proliferation through inducing G1 phase arrest in vitro and inhibit xenograft tumor growth in vivo. MiR‐129‐5p directly targeted the 3′ untranslated regions (3′ UTR) of HOXC10 mRNA and downregulated its expression. Importantly, miR‐129‐5p could reverse the oncogenic effect induced by HOXC10. We systemically screened the downstream target of HOXC10 by ChIP sequencing, and found that HOXC10 could transcriptionally regulate the expression of Cyclin D1 and facilitate G1/S cell cycle transition. Notably, high levels of HOXC10 and Cyclin D1 were related with poor prognosis of gastric cancer patients (n = 90). These findings reveal a novel role of miR‐129‐5p/HOXC10/Cyclin D1 axis in modulating cell cycle and gastric tumorigenesis, which might provide potential prognostic biomarkers and therapeutic targets for gastric cancer patients.

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“…Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide with about one million new cases reported every year, posing a burden to patients across the globe [1][2][3]. Lymph node metastasis (LNM) is the most common metastasis form of GC and the high mortality rate in GC is mostly influenced by formation of LNM.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a novel nomogram to predict overall survival in gastric cancer with lymph node metastasis

Mao¹,

Zhang²,

He³

et al. 2020

Int. J. Biol. Sci.

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Gastric cancer (GC) with lymph node metastasis (LNM) at diagnosis is associated with a unstable prognosis and indefinite survival times. The aim of the present study was to construct and validate a model for the Overall survival (OS) estimation for patients with LNM. The nomogram was constructed to predict the OS for LNM-positive GC using the primary group of 836 patients and validated using an independent cohort of 411 patients. Factors in the nomogram were identified by multivariate Cox hazard analysis. The predictive capability of nomogram was evaluated by calibration analysis and decision curve analysis. Multivariate analysis suggested that eight pre-treatment characteristics were used for developing the nomogram. In the primary cohort, the C-index for OS prediction was 0.788 (95% CI: 0.753-0.823), while in validation cohort, the C-index for OS prediction was 0.769 (95% CI: 0. 720-0.818). The calibration plot for the probability of OS and decision curve analyses showed an optimal agreement. Based on the nomogram, we could divided patients into three groups: low-risk group, middle-risk group and a high-risk group(p <0.001).Taken together, we have provided an easy-to-used and accurate tool for predicting OS, furthermore could be used for risk stratification of OS of LNM-positive GC patients.

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Gastric cancer: Basic aspects

Cited by 38 publications

References 52 publications

Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword

Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword

MiR‐129‐5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression

Development and validation of a novel nomogram to predict overall survival in gastric cancer with lymph node metastasis

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