A phase II multicenter trial assessing the efficacy and safety of first-line S-1 + ramucirumab in elderly patients with advanced/recurrent gastric cancer: KSCC1701

Kobayashi, Kazuma; Suyama, Koichi; Katsuya, Hiroo; Izawa, Naoki; Uenosono, Yoshikazu; Hu, Qingjiang; Kusumoto, Tetsuya; Otsu, Hajime; Orita, Hiroyuki; Kawanaka, Hirofumi; Shibao, Kazunori; Koga, S; Shimokawa, Mototsugu; Makiyama, Akitaka; Saeki, Hiroshi; Oki, Eiji; Baba, Hideo; Mori, Masaki

doi:10.1016/j.ejca.2022.02.028

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…In recent years, the microenvironment-targeted treatment of GC has begun to rise, including using various new drugs targeting FGFR [ 47 ], VEGFR [ 48 , 49 ], MMP9 [ 50 ] and TGF-β1 [ 51 ] for reshaping the matrix microenvironment [ 52 ]. Despite being a preliminary examination on showing the possible mechanism of INHBB’s impact on the microenvironment of GC, our study indicates that targeting fibroblast-cancer cell crosstalk is a promising alternative in GC clinical treatment by providing a well-explained possibility for the mechanism in place.…”

Section: Discussionmentioning

confidence: 99%

Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming

Jin,

Cai,

Wang

et al. 2023

J Exp Clin Cancer Res

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Background Important roles of INHBB in various malignancies are increasingly identified. The underlying mechanisms in gastric cancer (GC) microenvironment are still greatly unexplored. Methods The clinical significance of INHBB and the correlation between INHBB and p-p65 in GC were assessed through analyzing publicly available databases and human paraffin embedded GC tissues. The biological crosstalk of INHBB between GC cells and fibroblasts was explored both in vitro and in vivo. RNA-seq analyses were performed to determine the mechanisms which regulating fibroblasts reprogramming. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify the binding relationship of p65 and INHBB in GC cells. Results Our study showed that INHBB level was significantly higher in GC, and that increased INHBB was associated with poor survival. INHBB positively regulates the proliferation, migration, and invasion of GC cells in vitro. Also, activin B promotes the occurrence of GC by reprogramming fibroblasts into cancer-associated fibroblasts (CAFs). The high expression of INHBB in GC cells activates the NF-κB pathway of normal gastric fibroblasts by secreting activin B, and promotes fibroblasts proliferation, migration, and invasion. In addition, activin B activates NF-κB pathway by controlling TRAF6 autoubiquitination to induce TAK1 phosphorylation in fibroblasts. Fibroblasts activated by activin B can induce the activation of p65 phosphorylation of GC cells by releasing pro-inflammatory factors IL-1β. p65 can directly bind to the INHBB promoter and increase the INHBB transcription of GC cells, thus establishing a positive regulatory feedback loop to promote the progression of GC. Conclusions GC cells p65/INHBB/activin B and fibroblasts p65/IL-1β signal loop led to the formation of a whole tumor-promoting inflammatory microenvironment, which might be a promising therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming

Jin,

Cai,

Wang

et al. 2023

J Exp Clin Cancer Res

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Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers

Ji,

Chen,

et al. 2025

Critical Reviews in Oncology/Hematology

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Eriodictyol Suppresses Gastric Cancer Cells via Inhibition of PI3K/AKT Pathway

Shan

Zhang

et al. 2022

Pharmaceuticals

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Gastric cancer (GC) is among the five most common malignancies worldwide. Traditional chemotherapy cannot efficiently treat the disease and faces the problems of side effects and chemoresistance. Polygoni orientalis Fructus (POF), with flavonoids as the main bioactive compounds, exerts anti-cancer potential. In this study, we compared the anti-GC effects of the main flavonoids from POF and investigated the anti-cancer effects of eriodictyol towards GC both in vitro and in vivo. CCK-8 assays were performed to examine the inhibitory effects of common flavonoids from POF on GC cell viability. Colony formation assays were used to determine cell proliferation after eriodictyol treatment. Cell cycle distribution was analyzed using flow cytometry. Induction of apoptosis was assessed with Annexin V/PI staining and measurement of related proteins. Anti-cancer effects in vivo were investigated using a xenograft mouse model. Potential targets of eriodictyol were clarified by network pharmacological analysis, evaluated by molecular docking, and validated with Western blotting. We found that eriodictyol exhibited the most effective inhibitory effect on cell viability of GC cells among the common flavonoids from POF including quercetin, taxifolin, and kaempferol. Eriodictyol suppressed colony formation of GC cells and induced cell apoptosis. The inhibitory effects of eriodictyol on tumor growth were also validated using a xenograft mouse model. Moreover, no obvious toxicity was identified with eriodictyol treatment. Network pharmacology analysis revealed that PI3K/AKT signaling ranked first among the anti-GC targets. The molecular docking model of eriodictyol and PI3K was constructed, and the binding energy was evaluated. Furthermore, efficient inhibition of phosphorylation and activation of PI3K/AKT by eriodictyol was validated in GC cells. Taken together, our results identify eriodictyol as the most effective anti-GC flavonoids from POF and the potential targets of eriodictyol in GC. These findings suggest that eriodictyol has the potential to be a natural source of anti-GC agents.

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A phase II multicenter trial assessing the efficacy and safety of first-line S-1 + ramucirumab in elderly patients with advanced/recurrent gastric cancer: KSCC1701

Cited by 3 publications

References 19 publications

Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming

Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming

Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers

Eriodictyol Suppresses Gastric Cancer Cells via Inhibition of PI3K/AKT Pathway

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