scholarly journals Loss of CDC4/FBXW7 in Gastric Carinoma

2010 ◽  
Vol 32 (5-6) ◽  
pp. 347-359
Author(s):  
A. N. Milne ◽  
R. Leguit ◽  
W. E. Corver ◽  
F. H. M. Morsink ◽  
M. Polak ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Loss Of Heterozygosity ◽  
Tissue Microarrays ◽  
Suppressor Gene ◽  
Gastric Carcinogenesis ◽  
Gastric Carcinoma Cell ◽  
Gastric Carcinomas ◽  
Gastric Cancers ◽  
Tumor Types

Background: CDC4/FBXW7, encoding a ubiquitin ligase, maps to 4q32 and has been implicated as a tumor suppressor gene and therapeutic target in many tumor types. Mutations in colonic adenomas, and the frequent losses on 4q described in gastric cancer prompt speculation about the role of CDC4/FBXW7 in gastric carcinogenesis.Methods: We assessed the role of CDC4/FBXW7 in gastric cancer, through loss of heterozygosity (LOH) and multiplex ligation-dependent probe amplification (MLPA) on 47 flow-sorted gastric carcinomas including early-onset gastric cancers (EOGC) and xenografted conventional gastric carcinomas. Ploidy analysis was carried out on 39 EOGCs and immunohistochemistry of CDC4/FBXW7 and its substrates c-myc, c-jun, Notch and cyclin E was performed on 204 gastric carcinomas using tissue microarrays (TMAs). Sequence analysis of CDC4/FBXW7 was carried out on gastric carcinoma cell lines and xenografts.Results: Loss of heterozygosity of CDC4/FBXW7 occurred in 32% of EOGCs, and correlated with loss of expression in 26%. Loss of expression was frequent in both EOGC and conventional gastric cancers. No CDC4/FBXW7 mutations were found and loss of CDC4/FBXW7 did not correlate with ploidy status. There was a significant correlation between loss of CDC4/FBXW7 expression and upregulation of c-myc.Conclusions: Loss of CDC4/FBXW7 appears to play a role in both EOGC and conventional gastric carcinogenesis, and c-myc overexpression is likely to be an important oncogenic consequence of CDC4/FBXW7 loss.

scholarly journals Types of Gastric Carcinomas

2018 ◽  
Vol 19 (12) ◽  
pp. 4109 ◽  
Author(s):  
Helge Waldum ◽  
Reidar Fossmark
Keyword(s):  
Gastric Cancer ◽  
Stem Cell ◽  
Gastric Carcinogenesis ◽  
Cell Of Origin ◽  
Gastric Carcinomas ◽  
Ecl Cell ◽  
Cells Of Origin ◽  
Increased Risk

Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for Helicobacter pylori as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.

scholarly journals The Role of PPARγinHelicobacter pyloriInfection and Gastric Carcinogenesis

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jong-Min Lee ◽  
Sung Soo Kim ◽  
Young-Seok Cho
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Current Knowledge ◽  
Mucosal Injury ◽  
Gastric Carcinogenesis ◽  
Etiologic Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
H Pylori

Peroxisome proliferator-activated receptorγ(PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγplays an important role in gastric mucosal injury due toHelicobacter pylori(H. pylori). AsH. pyloriinfection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγinH. pyloriinfection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγinH. pyloriinfection and its related gastric carcinogenesis.

scholarly journals Lysyl Oxidase Is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers

2004 ◽  
Vol 64 (18) ◽  
pp. 6410-6415 ◽  
Author(s):  
Atsushi Kaneda ◽  
Kuniko Wakazono ◽  
Tetsuya Tsukamoto ◽  
Naoko Watanabe ◽  
Yukiko Yagi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Loss Of Heterozygosity ◽  
Lysyl Oxidase ◽  
Suppressor Gene ◽  
Gastric Cancers

scholarly journals Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis—what is currently known?

2021 ◽  
Author(s):  
Karolina Kaźmierczak-Siedlecka ◽  
Agnieszka Daca ◽  
Giandomenico Roviello ◽  
Martina Catalano ◽  
Karol Połom
Keyword(s):  
Gastric Cancer ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Gastric Carcinogenesis ◽  
Point Of View ◽  
Molecular Techniques ◽  
Nitroso Compounds ◽  
Gastric Microbiota ◽  
Development Of Gastric Cancer

AbstractCurrently, gastric cancer is one of the leading death-related cancer globally. The etiopathogenesis of gastric cancer is multifactorial and includes among others dysbiotic alterations of gastric microbiota. Molecular techniques revealed that stomach is not a sterile organ and it is resides with ecosystem of microbes. Due to the fact that the role of Helicobacter pylori infection in development of gastric cancer is established and well-studied, this paper is mainly focused on the role of other bacterial as well as viral and fungal gut microbiota imbalance in gastric carcinogenesis. Notably, not only the composition of gastric microbiota may play an important role in development of gastric cancer, but also its activity. Microbial metabolites, such as short-chain fatty acids, polyamines, N-nitroso compounds, and lactate, may significantly affect gastric carcinogenesis. Therefore, this paper discussed aforementioned aspects with the interdisciplinary insights (regarding also immunological point of view) into the association between gut microbiome and gastric carcinogenesis based on up-to-date studies.

scholarly journals Introduction to DOK2 and its Potential Role in Cancer

2021 ◽  
pp. 671-685
Author(s):  
P SUN ◽  
R LI ◽  
Y MENG ◽  
S XI ◽  
Q WANG ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Potential Role ◽  
Suppressor Gene ◽  
Modern Medicine ◽  
Mechanisms Of Action ◽  
Multiple Tumor ◽  
Tyrosine Kinase 2 ◽  
Prevention And Treatment ◽  
Tumor Types

Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways.

Fatty acid synthase is a prognostic marker and associated with immune infiltrating in gastric cancers precision medicine

2020 ◽  
Vol 14 (3) ◽  
pp. 185-199
Author(s):  
Yangying Zhou ◽  
Weiping Su ◽  
Huan Liu ◽  
Taili Chen ◽  
Naseruddin Höti ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Survival Outcome ◽  
De Novo Synthesis ◽  
Bioinformatics Analyses ◽  
Key Enzyme ◽  
Tumor Types

Aim: Fatty acid synthase (FASN), a key enzyme for de novo synthesis of fatty acids, has been identified as an oncogene in some tumor types; however, the function of FASN in gastric cancer (GC) is poorly elucidated. Method: Integrative bioinformatics analyses were performed to unveil the role of FASN in tumor progression and cancer-associated immunology of GC. Result: FASN was overexpressed in the GC tissues and correlated with an inferior survival outcome, and largely contributed to the carcinogenesis of GC. Moreover, FASN expression was closely associated with the immune-infiltrating levels of CD8+ T, CD4+ T, neutrophils, macrophages and dendritic cells. Conclusion: FASN was closely associated with GC and may be involved in the tumorigenesis and cancer–immune interactions, and could be a promising prognostic and therapeutic biomarker in GC.

scholarly journals The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma

2019 ◽  
Vol 12 ◽  
pp. 175628481986976 ◽  
Author(s):  
Gagandeep Brar ◽  
Manish A. Shah
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Response To Treatment ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Tumor Types

Gastric cancer is a leading cause of cancer-related death worldwide. Recent evidence suggests that gastric cancer is a complex and heterogenous disease with emerging subtypes shown to affect response to treatment and survival. Immunotherapy is an advancing field and immune checkpoint inhibitors have become standard treatment options in numerous tumor types. In this review, we discuss the current and evolving use of checkpoint blockade, focusing on the anti-PD-1 inhibitor, pembrolizumab, for use in advanced gastric and gastroesophageal cancers.

scholarly journals Targeting the Oncogenic FGF-FGFR Axis in Gastric Carcinogenesis

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 637 ◽  
Author(s):  
Jinglin Zhang ◽  
Patrick M. K. Tang ◽  
Yuhang Zhou ◽  
Alfred S. L. Cheng ◽  
Jun Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Therapeutic Strategy ◽  
Somatic Mutations ◽  
Synergistic Effects ◽  
Gastric Carcinogenesis ◽  
Wide Spread ◽  
Oncogenic Pathways ◽  
The World ◽  
Clinical Correlations

Gastric cancer (GC) is one of the most wide-spread malignancies in the world. The oncogenic role of signaling of fibroblast growing factors (FGFs) and their receptors (FGFRs) in gastric tumorigenesis has been gradually elucidated by recent studies. The expression pattern and clinical correlations of FGF and FGFR family members have been comprehensively delineated. Among them, FGF18 and FGFR2 demonstrate the most prominent driving role in gastric tumorigenesis with gene amplification or somatic mutations and serve as prognostic biomarkers. FGF-FGFR promotes tumor progression by crosstalking with multiple oncogenic pathways and this provides a rational therapeutic strategy by co-targeting the crosstalks to achieve synergistic effects. In this review, we comprehensively summarize the pathogenic mechanisms of FGF-FGFR signaling in gastric adenocarcinoma together with the current targeted strategies in aberrant FGF-FGFR activated GC cases.

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