ArticleNeoplasia (New York, N.Y.)2016
Inhibition of Rho-Associated Kinase 1/2 Attenuates Tumor Growth in Murine Gastric Cancer.
Article in Neoplasia (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Synergistic Interactions Between Medicinal Plant Bioactive and Standard Chemotherapy in Gastric Cancer: Preclinical Evidence and Translational Pitfalls.Biomedicines · 2026Review
- Opposing effects of Rho-associated coiled-coil kinase 1 (ROCK1) and ROCK2 in TGF-β-SMAD signaling.Cell communication and signaling : CCS · 2026Article
- Unlocking drug development: the distinctive roles of PET and SPECT imaging from molecular kinetics to therapeutic response.Archives of pharmacal research · 2026Review
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
- Rho/ROCK Pathway as a Therapeutic Target in Multiple Diseases.International journal of drug discovery and pharmacology · 2025Article
- An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells.Nature communications · 2024Article
- Functional antagonism between CagA and DLC1 in gastric cancer.Cell death discovery · 2022Article
- Multi-omics profiling of collagen-induced arthritis mouse model reveals early metabolic dysregulation via SIRT1 axis.Scientific reports · 2022Article
- The dawn of precision medicine in diffuse-type gastric cancer.Therapeutic advances in medical oncology · 2022Review
- Research on the Mechanism and Prevention of Hypertension Caused by Apatinib Through the RhoA/ROCK Signaling Pathway in a Mouse Model of Gastric Cancer.Frontiers in cardiovascular medicine · 2022Article
- A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific KCancers · 2021Article
- Multiplex enzyme activity imaging by MALDI-IMS of substrate library conversions.Scientific reports · 2020Article
- Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib in Liver Metastases of Gastrointestinal Stromal Tumors.Scientific reports · 2019Article
- MiR-381 functions as a tumor suppressor in gastric cancer by targeting ROCK2.International journal of clinical and experimental pathology · 2019Article
- Spatial Distribution of Endogenous Tissue Protease Activity in Gastric Carcinoma Mapped by MALDI Mass Spectrometry Imaging.Molecular & cellular proteomics : MCP · 2019Article
- Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging.Analytical chemistry · 2018Article
- Article
- Interactive Visual Exploration of 3D Mass Spectrometry Imaging Data Using Hierarchical Stochastic Neighbor Embedding Reveals Spatiomolecular Structures at Full Data Resolution.Journal of proteome research · 2018Article
- The Rho GTPase signalling pathway in urothelial carcinoma.Nature reviews. Urology · 2018Review
- Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging in the Study of Gastric Cancer: A Mini Review.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer (GC) remains a malignant disease with high mortality. Patients are frequently diagnosed in advanced stages where survival prognosis is poor. Thus, there is high medical need to find novel drug targets and treatment strategies. Recently, the comprehensive molecular characterization of GC subtypes revealed mutations in the small GTPase RHOA as a hallmark of diffuse-type GC. RHOA activates RHO-associated protein kinases (ROCK1/2) which regulate cell contractility, migration and growth and thus may play a role in cancer. However, therapeutic benefit of RHO-pathway inhibition in GC has not been shown so far. The ROCK1/2 inhibitor 1-(5-isoquinoline sulfonyl)-homopiperazine (HA-1077, fasudil) is approved for cerebrovascular bleeding in patients. We therefore investigated whether fasudil (i.p., 10 mg/kg per day, 4 times per week, 4 weeks) inhibits tumor growth in a preclinical model of GC. Fasudil evoked cell death in human GC cells and reduced the tumor size in the stomach of CEA424-SV40 TAg transgenic mice. Small animal PET/CT confirmed preclinical efficacy. Mass spectrometry imaging identified a translatable biomarker for mouse GC and suggested rapid but incomplete in situ distribution of the drug to gastric tumor tissue. RHOA expression was increased in the neoplastic murine stomach compared with normal non-malignant gastric tissue, and fasudil reduced (auto) phosphorylation of ROCK2 at THR249 in vivo and in human GC cells in vitro. In sum, our data suggest that RHO-pathway inhibition may constitute a novel strategy for treatment of GC and that enhanced distribution of future ROCK inhibitors into tumor tissue may further improve efficacy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.