scholarly journals MEK Inhibition Suppresses Metastatic Progression of KRAS ‐Mutated Gastric Cancer

2021 ◽  
Author(s):  
Juntaro Yamasaki ◽  
Yuki Hirata ◽  
Yuji Otsuki ◽  
Kentaro Suina ◽  
Yoshiyuki Saito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Metastatic Progression ◽  
Mek Inhibition

Prolonged MEK inhibition leads to acquired resistance and increased invasiveness in KRAS mutant gastric cancer

2018 ◽  
Vol 507 (1-4) ◽  
pp. 311-318 ◽  
Author(s):  
Kyoung-Min Choi ◽  
Eunji Cho ◽  
Eunjung Kim ◽  
Jong Hwan Shin ◽  
Minju Kang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Acquired Resistance ◽  
Mek Inhibition

Relationship of novel genetically engineered mouse and the epithelial-mesenchymal transition in the metastastic progression of gastric cancers.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 3-3
Author(s):  
Hark K. Kim ◽  
Jun Won Park ◽  
Jeffrey E. Green
Keyword(s):  
Gastric Cancer ◽  
Lung Metastases ◽  
Genetically Engineered ◽  
Conditional Knockout ◽  
Metastatic Progression ◽  
Diffuse Type ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Gastric Adenocarcinomas ◽  
E Cadherin

3 Background: By creating mice deficient in E-cadherin, Smad4, and p53, we evaluated whether and how Cdh1 heterozygosity may accelerate the development and progression of gastric cancer, in combination with loss of Smad4 and p53. Methods: Compound conditional knockout mice of Smad4, p53, and E-cadherin were mated with Pdx-1-Cre transgenic mice. Offsprings were monitored for the development of gastric adenocarcinomas. Results: Gastric adenocarcinomas spontaneously arose in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice and recapitulated human diffuse type gastric cancers in histopathology. Gastric adenocarcinoma was more frequent in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice than in Pdx-1-Cre;Smad4F/F;Trp53F/F mice. When compared to Pdx-1-Cre;Trp53F/F;Cdh1F/F mice, Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice developed gastric adenocarcinomas more rapidly, suggesting that Smad4 and E-cadherin cooperate to constrain the development of gastric adenocarcinomas. Lung metastases were identified in three Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice, but not in the other genotypes. The epithelial-to-mesenchymal transition (EMT), characterized by increased vimentin expression, was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the suppression of EMT by E-cadherin or Smad4 may reduce metastatic signaling pathways in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. Conclusions: Loss of E-cadherin and Smad4 cooperate with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human diffuse type gastric cancer. Thus, our novel genetically-engineered mouse models reveal the importance of EMT in the metastatic progression of gastric cancers, providing a unique model to test agents targeting the metastatic progression in gastric cancers.

scholarly journals EGFR and HER2 signals play a salvage role in MEK1-mutated gastric cancer after MEK inhibition

2015 ◽  
Vol 47 (2) ◽  
pp. 499-505 ◽  
Author(s):  
TAKURO MIZUKAMI ◽  
YOSUKE TOGASHI ◽  
SHUNSUKE SOGABE ◽  
ERI BANNO ◽  
MASATO TERASHIMA ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mek Inhibition

scholarly journals Reduced phosphorylation of ribosomal protein S6 is associated with sensitivity to MEK inhibition in gastric cancer cells

2016 ◽  
Vol 107 (12) ◽  
pp. 1919-1928 ◽  
Author(s):  
Yuka Hirashita ◽  
Yoshiyuki Tsukamoto ◽  
Kazuyoshi Yanagihara ◽  
Shoichi Fumoto ◽  
Naoki Hijiya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Ribosomal Protein ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Mek Inhibition ◽  
Ribosomal Protein S6

MEK inhibition overcomes everolimus resistance in gastric cancer

2020 ◽  
Vol 85 (6) ◽  
pp. 1079-1087
Author(s):  
Hongfang Liu ◽  
Yang Yao ◽  
Juan Zhang ◽  
Jing Li
Keyword(s):  
Gastric Cancer ◽  
Mek Inhibition

scholarly journals EGFR and HER2 signals play a salvage role in MEK1-mutated gastric cancer after MEK inhibition

2015 ◽  
Vol 26 ◽  
pp. vii129
Author(s):  
Takuro Mizukami ◽  
Yosuke Togashi ◽  
Shunsuke Sogabe ◽  
Marco A de Velasco ◽  
Kazuko Sakai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mek Inhibition

Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer

2009 ◽  
Vol 136 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Yuan-Yu Wang ◽  
Zai-Yuan Ye ◽  
Zhong-Sheng Zhao ◽  
Hou-Quan Tao ◽  
Shu-Guang Li
Keyword(s):  
Gastric Cancer ◽  
Systems Biology ◽  
Metastatic Progression

scholarly journals Enhanced G1 arrest and apoptosis via MDM4/MDM2 double knockdown and MEK inhibition in wild‑type TP53 colon and gastric cancer cells with aberrant KRAS signaling

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoxuan Wang ◽  
Yoshiyuki Yamamoto ◽  
Mamiko Imanishi ◽  
Xiaochen Zhang ◽  
Masashi Sato ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
G1 Arrest ◽  
Wild Type ◽  
Gastric Cancer Cells ◽  
Mek Inhibition

Down-Regulation of CXCL12 by DNA Hypermethylation and Its Involvement in Gastric Cancer Metastatic Progression

2011 ◽  
Vol 57 (3) ◽  
pp. 650-659 ◽  
Author(s):  
Yu Zhi ◽  
Jing Chen ◽  
Shuanglong Zhang ◽  
Xiaojing Chang ◽  
Jingguo Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Metastatic Progression ◽  
Dna Hypermethylation ◽  
Down Regulation

Ultrastructural Cytochemical Study of Human Gastric Cancer: Observation of AKP ase,ACP ase,G6P ase,TPP ase and CO ase

1990 ◽  
Vol 48 (3) ◽  
pp. 254-255
Author(s):  
Dong Yuming ◽  
Yang Guanglin ◽  
Du Wei Dong ◽  
Xu Ai Liam
Keyword(s):  
Gastric Cancer ◽  
Gastric Epithelium ◽  
Human Gastric Cancer ◽  
Electron Microscopic ◽  
Cytochemical Study ◽  
Electron Microscopic Cytochemistry ◽  
Cytochemical Reaction ◽  
Set Up ◽  
Cancer Tissues ◽  
Cytochemical Technique

The activities and distributions of AKPase ,ACPase,G6Pase,TPPase and COase in human normal gastric mucosa and gastric cancer tissues were studied histochemically at light microscopic level. These enzymes are the marker enzymes of cell membrane lysosome endoplasmic reticulum, Golgi apparatus and mitochondrion objectively. On the basis of the research we set up a special ultrastructural cytochemical technique and first researched into gastric cancer domesticly. Ultrastructural cytochemistry is also called electron microscopic cytochemistry. This new technique possesses both the sensitivity of cytochemical reaction andi the high resolution of electron microscope. It is characterized by direct observation,exact localization and the combination morphology with function.The distributions of AKPase,ACPase,G6Pase,TPPase and COase in 14 cases of gastric cancer and 1 case of gastric Denign lesion were studied ultrastructurally. The results showed: 1. normal gastric epithelium had no AKPase reaction. The reaction of ACPase,G6Pase,TPPase and Coase were found in the corresponding organella, which were consistent with their function.

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